Minimally invasive treatments are essential for patients with liver tumors that do not respond to chemotherapy and for patients with inoperable liver cancers. Radiofrequency (RF) and microwave (MW) ablation techniques are interstitial, focal therapies that are being used with increasing frequency for these cases. Image guidance for placement of RF or MW probes and for initial assessments of treated volumes is essential for the success of these procedures. We and others have demonstrated that ultrasound based strain and modulus imaging are promising for accurately depicting the treated volumes in ablation procedures. Initial assessments for superficial structures demonstrate high image contrast of ablated regions. Our research will develop and evaluate a novel strain imaging method termed """"""""electrode displacement elastography,"""""""" or EDE, to monitor minimally invasive ablative treatments and delineate the zone of necrosis regardless of the depth of treatment. We will initially test the effectiveness of EDE using echo data acquired with conventional curvilinear and phased arrays. This will be done by imaging custom tissue-mimicking phantoms with Young's Modulus values equivalent to that of liver tissue to determine reliability of mapping out ablated and partially ablated regions for various EDE acquisition parameters. Finite element analysis (FEA) to model deformations induced by RF/microwave displacements will be performed to better understand these experimental results. We then will evaluate 2D EDE on human patients, acquiring data at typical imaging depths and for various liver states, i.e. cirrhotic liver for hepatocellular carcinoma (HCC) and softer livers with stiffer tumors for metastases. Comparisons between EDE strain and follow-up X-ray CT images will provide crucial information on the effectiveness of EDE strain images to delineate the zone of necrosis. We will then develop and test bi-plane and three-dimensional (3D) volumetric EDE strain and modulus imaging using a 2D matrix phased array transducer. Accuracy of ablation boundary delineation for different echo data acquisition conditions will be determined using tissue-mimicking phantoms. In-vivo studies will then be conducted to test bi-plane and 3D EDE for strain and modulus imaging both on a wood-chuck HCC model and a rabbit VX2 metastases model to evaluate depiction and delineation of cancers before and after ablation therapy. Comparisons of the strain and modulus images with histopathology using light microscopy of ablated tissue will be performed. Finally, a pilot study will be performed using percutaneous bi-plane and 3D EDE on human patients. Successful completion of these studies will pave the way for clinical trials using EDE for monitoring minimally invasive ablative therapies. Incidence of HCC has doubled in the last decade, with a mortality rate of 3-6 months without treatment. The clinical significance of accurate ultrasound-based guidance for ablation treatments will be high, both in terms of reducing patient morbidity and of lowering treatment costs.

Public Health Relevance

We propose to develop a noninvasive and nonionizing approaches using ultrasound based strain and modulus imaging to monitor minimally invasive ablative therapies such as radiofrequency and microwave ablation for treating primary liver tumors and metastases. Treatment monitoring is essential since local recurrence rates after RF ablative therapy are as high as 34-55%, due in part to the inability to accurately visualize and delineate the zone of necrosis in the region treated.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA112192-07
Application #
8691741
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Tandon, Pushpa
Project Start
2004-12-01
Project End
2018-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Physics
Type
Schools of Medicine
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
Yang, Wenjun; Varghese, Tomy; Ziemlewicz, Timothy et al. (2017) Delineation of Post-Procedure Ablation Regions with Electrode Displacement Elastography with a Comparison to Acoustic Radiation Force Impulse Imaging. Ultrasound Med Biol 43:1953-1962
Samimi, Kayvan; Varghese, Tomy (2017) Lower Bound on Estimation Variance of the Ultrasonic Attenuation Coefficient Using the Spectral-Difference Reference-phantom Method. Ultrason Imaging 39:151-171
Meshram, N H; Varghese, T; Mitchell, C C et al. (2017) Quantification of carotid artery plaque stability with multiple region of interest based ultrasound strain indices and relationship with cognition. Phys Med Biol 62:6341-6360
Samimi, Kayvan; White, James K; Brace, Christopher L et al. (2017) Monitoring Microwave Ablation of Ex Vivo Bovine Liver Using Ultrasonic Attenuation Imaging. Ultrasound Med Biol 43:1441-1451
Ingle, Atul; Varghese, Tomy; Sethares, William A (2017) Efficient 3-D Reconstruction in Ultrasound Elastography via a Sparse Iteration Based on Markov Random Fields. IEEE Trans Ultrason Ferroelectr Freq Control 64:491-499
Wang, Xiao; Jackson, Daren C; Mitchell, Carol C et al. (2016) Classification of Symptomatic and Asymptomatic Patients with and without Cognitive Decline Using Non-invasive Carotid Plaque Strain Indices as Biomarkers. Ultrasound Med Biol 42:909-18
Ma, Chi; Wang, Xiao; Varghese, Tomy (2016) Segmental Analysis of Cardiac Short-Axis Views Using Lagrangian Radial and Circumferential Strain. Ultrason Imaging 38:363-383
Samimi, Kayvan; Varghese, Tomy (2016) Optimum Diffraction-Corrected Frequency-Shift Estimator of the Ultrasonic Attenuation Coefficient. IEEE Trans Ultrason Ferroelectr Freq Control :
Peng, Bo; Wang, Yu; Yang, Wenjun et al. (2016) Relative Elastic Modulus Imaging Using Sector Ultrasound Data for Abdominal Applications: An Evaluation of Strategies and Feasibility. IEEE Trans Ultrason Ferroelectr Freq Control 63:1432-40
Yang, Wenjun; Ingle, Atul; Varghese, Tomy (2016) Comparison of three dimensional strain volume reconstructions using SOUPR and wobbler based acquisitions: A phantom study. Med Phys 43:1615

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